Potassium Phosphate, Tribasic → 4-(3'-fluoro-3-methoxy-[1,1'-biphenyl]-4-yl)-N-(1,2,4-thiadiazol-5-yl)quinazoline-7-sulfonamide

HRID 1473688Notes

Reaction equation

HRID 1473688 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18]([NH:21][C:22]4[S:26][N:25]=[CH:24][N:23]=4)(=[O:20])=[O:19])=[CH:15][CH:16]=3)[N:11]=[CH:10][N:9]=2)=[C:4]([O:27][CH3:28])[CH:3]=1.[F:29][C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][CH:35]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>>[F:29][C:30]1[CH:35]=[C:34]([C:2]2[CH:7]=[CH:6][C:5]([C:8]3[C:17]4[C:12](=[CH:13][C:14]([S:18]([NH:21][C:22]5[S:26][N:25]=[CH:24][N:23]=5)(=[O:20])=[O:19])=[CH:15][CH:16]=4)[N:11]=[CH:10][N:9]=3)=[C:4]([O:27][CH3:28])[CH:3]=2)[CH:33]=[CH:32][CH:31]=1

Participants

5

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27339863-Fluorophenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 866877704-(4-chloro-2-methoxyphenyl)-N-(1,2,4-thiadiazol-5-yl)quinazoline-7-sulfonamide

Product 1

HCID 866877724-(3'-fluoro-3-methoxy-[1,1'-biphenyl]-4-yl)-N-(1,2,4-thiadiazol-5-yl)quinazoline-7-sulfonamide

Procedure

A vial was charged with 4-(4-chloro-2-methoxyphenyl)-N-(1,2,4-thiadiazol-5-yl)quinazoline-7-sulfonamide (Example 524; 0.050 g, 0.115 mmol), (3-fluorophenyl)boronic acid (0.032 g, 0.230 mmol), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (2.365 mg, 5.76 μmol), chloro(2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]palladium(ii) dichloromethane (4.36 mg, 5.76 μmol), and potassium phosphate (0.073 g, 0.346 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (0.524 ml) and Water (0.052 ml) were added in sequence. The vial was sealed and microwaved at 80° C. for three hours. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (RediSep Gold 12 g, gradient elution 0-10% MeOH:DCM) to afford 4-(3′-fluoro-3-methoxy-[1,1′-biphenyl]-4-yl)-N-(1,2,4-thiadiazol-5-yl)quinazoline-7-sulfonamide as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ=9.47 (s, 1H), 8.39 (d, J=1.7 Hz, 1H), 8.34 (s, 1H), 8.00-7.97 (m, 1H), 7.91-7.87 (m, 1H), 7.75-7.72 (m, 1H), 7.72-7.68 (m, 2H), 7.61-7.49 (m, 4H), 7.31-7.23 (m, 1H), 3.81 (s, 3H). m/z (ESI) 494.2 (M+H)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. addition1,4-dioxane (0.524 ml) and Water (0.052 ml) were added in sequence
  3. customThe vial was sealed
  4. custommicrowaved at 80° C. for three hours
  5. additionThe reaction was diluted with ethyl acetate
  6. washwashed with water
  7. extractionThe aqueous layer was extracted with ethyl acetate
  8. dry with materialthe combined organic layers were dried with sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe material was purified via column chromatography (RediSep Gold 12 g, gradient elution 0-10% MeOH:DCM)

Sources & evidence

ORD record
ord-e0fa8ad1bd9945c9b6f40cb057461e04
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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